The long-term effect of maternal dietary protein restriction on 5-HT1A receptor function and behavioral responses to stress in adulthood

Maternal nutrition impacts fetal development, and may play a role in determining resilience to stress and vulnerability to stress-precipitated psychiatric disorders, such as anxiety and depression. In this study, we examined the effect of a reduction in maternal dietary protein during pregnancy on the brain neurochemistry and behavior of offspring. We focused specifically on the serotonin system, the 5-HT1A receptor and the responsivity of offspring as adults to stress. Dams were fed either a low protein diet (10% protein by weight) or isocaloric control diet (20% protein by weight). The low protein diet did not alter maternal food intake and body weight, or litter size and the average birth weight of male or female littermates. 5-HT1A receptor function, as measured by quantitative autoradiography of 8-OH-DPAT (1 μM)-stimulated [35S]GTPγS binding, was markedly reduced in hippocampus of weanling female, but not male offspring (postnatal day, PND 21) of dams fed the low protein diet. The number of serotonergic cell bodies in the rostral raphe, and 5-HT metabolism in the limbic system of weanling offspring was not altered by maternal low protein diet. The deficit in hippocampal 5-HT1A receptor function observed in weanling female offspring persisted into adulthood (PND 112), and was accompanied by an increased sensitivity to stress, specifically increased immobility during a 15-minute forced swim challenge and increased anorexia following 30-minute restraint (PND 97-100). The present work begins to uncover important future directions for understanding the early developmental origins of resilience to stress, and factors that may put individuals at greater risk for stress-related psychiatric disorders.